Neural Effects of Positive and Negative Incentives During Marijuana Withdrawal.

Neural Effects of Positive and Negative Incentives during Marijuana Withdrawal.

PLoS One. 2013; 8(5): e61470
Filbey FM, Dunlop J, Myers US

In spite of evidence suggesting two possible mechanisms related to drug-seeking behavior, namely reward-seeking and harm avoidance, much of the addiction literature has focused largely on positive incentivization mechanisms associated with addiction. In this study, we examined the contributing neural mechanisms of avoidance of an aversive state to drug-seeking behavior during marijuana withdrawal. To that end, marijuana users were scanned while performing the monetary incentive delay task in order to assess positive and negative incentive processes. The results showed a group x incentive interaction, such that marijuana users had greater response in areas that underlie reward processes during positive incentives while controls showed greater response in the same areas, but to negative incentives. Furthermore, a negative correlation between withdrawal symptoms and response in the amygdala during negative incentives was found in the marijuana users. These findings suggest that although marijuana users have greater reward sensitivity and less harm avoidance than controls, that attenuated amygdala response, an area that underlies fear and avoidance, was present in marijuana users with greater marijuana withdrawal symptoms. This is concordant with models of drug addiction that involve multiple sources of reinforcement in substance use disorders, and suggests the importance of strategies that focus on respective mechanisms. HubMed – addiction


Differential effects of cocaine on histone posttranslational modifications in identified populations of striatal neurons.

Proc Natl Acad Sci U S A. 2013 May 20;
Jordi E, Heiman M, Marion-Poll L, Guermonprez P, Cheng SK, Nairn AC, Greengard P, Girault JA

Drugs of abuse, such as cocaine, induce changes in gene expression and epigenetic marks including alterations in histone posttranslational modifications in striatal neurons. These changes are thought to participate in physiological memory mechanisms and to be critical for long-term behavioral alterations. However, the striatum is composed of multiple cell types, including two distinct populations of medium-sized spiny neurons, and little is known concerning the cell-type specificity of epigenetic modifications. To address this question we used bacterial artificial chromosome transgenic mice, which express EGFP fused to the N-terminus of the large subunit ribosomal protein L10a driven by the D1 or D2 dopamine receptor (D1R, D2R) promoter, respectively. Fluorescence in nucleoli was used to sort nuclei from D1R- or D2R-expressing neurons and to quantify by flow cytometry the cocaine-induced changes in histone acetylation and methylation specifically in these two types of nuclei. The two populations of medium-sized spiny neurons displayed different patterns of histone modifications 15 min or 24 h after a single injection of cocaine or 24 h after seven daily injections. In particular, acetylation of histone 3 on Lys 14 and of histone 4 on Lys 5 and 12, and methylation of histone 3 on Lys 9 exhibited distinct and persistent changes in the two cell types. Our data provide insights into the differential epigenetic responses to cocaine in D1R- and D2R-positive neurons and their potential regulation, which may participate in the persistent effects of cocaine in these neurons. The method described should have general utility for studying nuclear modifications in different types of neuronal or nonneuronal cell types. HubMed – addiction


Withdrawal syndrome caused by naltrexone in opioid abusers.

Hum Exp Toxicol. 2013 May 20;
Hassanian-Moghaddam H, Afzali S, Pooya A

Study objective: Naltrexone is a competitive opioid receptor antagonist acting at the µ- and k-opioid receptors that blocks the euphoric effects of exogenous administered opioids. When used in opioid-dependent patients, naltrexone can cause acute and severe withdrawal symptoms.Methods: This was a cross-sectional study conducted from December 2007 to March 2008 and consisted of patients who had used naltrexone accidentally or deliberately and were referred to Loghman-Hakim Poison Hospital, Tehran, Iran. All symptoms and signs were assessed and the relationship between the dose of naltrexone, opioid dependence, and outcome was evaluated.Results: In 132 patients referred to our hospital, the most frequently reported symptoms and signs occurring in more than 10% of patients were agitation (96.2%), altered level of consciousness (38.6%), nausea (28%), vomiting (27.3%), abdominal pain (24.2%), diarrhea (16.7%), bone and muscle pain (15.9%), tachycardia (12.9%), and dilated pupils (11.4%). Being the most prominent symptom, the agitation was the most difficult aspect of withdrawal to manage. Except for agitation, no relationship was found between the presence of these symptoms and the dose of naltrexone used. Outcome of the patients (classified as complete recovery, partial recovery, death, and no follow-up) was related to the substance of addiction (p < 0.05) but not to the naltrexone dose.Conclusion: Emergency physicians should be aware of the potential for severe agitation from naltrexone-precipitated hyperacute withdrawal and its appropriate management. Opioid-dependent patients who wish to continue withdrawal and abstinence must be encouraged to visit trained physicians and be warned about misuse of naltrexone. HubMed – addiction


Understanding the Needs of Colorectal Cancer Patients during the Pre-diagnosis Phase.

J Cancer Educ. 2013 May 21;
Wiljer D, Walton T, Gilbert J, Boucher A, Ellis PM, Schiff S, Sellick SM, Simunovic M, Kennedy E, Urowitz S

Patients with colorectal cancer (CRC) face a number of challenges leading up to diagnosis; however, research is limited regarding their specific needs during the pre-diagnosis period. A multicenter cross-sectional survey was conducted to elicit information about the CRC experience during the pre-diagnosis phase. Across the three sites, 104 eligible patients were approached, and 82 patients completed the survey, for a total response rate of 78.9 %. The needs most identified by participants during the pre-diagnosis period were informational (31.6 %) and emotional (20.3 %) needs; social needs were rated as the least important need for these patients (7 %). The majority (84.0 %) reported that these needs were met. Participants reported feeling shocked or overwhelmed on learning of their diagnosis (57.1 %) and high levels of anxiety during this time (40.0 %). The majority (77.9 %) of participants reported that they were not directed to any resources to help address their anxiety. Informational and emotional needs are identified as the most important needs during the pre-diagnosis phase, and for most these needs are being met; however, some participants are experiencing high levels of anxiety without access to appropriate resources. Further work is required to understand the optimal mechanisms to address identified needs during this pre-diagnosis period and to assess the potential benefits and costs of addressing these needs. HubMed – addiction


Genetic Risk for Nicotine Dependence in the Cholinergic System and Activation of the Brain Reward System in Healthy Adolescents.

Neuropsychopharmacology. 2013 May 21;
Nees F, Witt SH, Lourdusamy A, Vollstädt-Klein S, Steiner S, Poustka L, Banaschewski T, Barker GJ, Büchel C, Conrod PJ, Frank J, Gallinat J, Garavan H, Heinz A, Ittermann B, Loth E, Mann K, Artiges E, Paus T, Pausova Z, Smolka MN, Struve M, Schumann G, Rietschel M, Flor H

Genetic variation in a genomic region on chromosome 15q25.1, which encodes the alpha5, alpha3, and beta4 subunits of the cholinergic nicotinic receptor genes, confers risk to smoking and nicotine dependence (ND). Neural reward-related responses have previously been identified as important factors in the development of drug dependence involving ND. Applying an imaging genetics approach in two cohorts (N=487; N=478) of healthy non-smoking adolescents we aimed to elucidate the impact of genome-wide significant smoking-associated variants in the CHRNA5-CHRNA3-CHRNB4 gene cluster on reward-related neural responses in central regions such as the striatum, orbitofrontal and anterior cingulate cortex and personality traits related to addiction. In both samples carriers of the rs578776 GG compared with AG/AA genotype showed a significantly lower neural response to reward outcomes in the right ventral and dorsal anterior cingulate cortex but not the striatum or the orbitofrontal cortex. Rs578776 was unrelated to neural reward anticipation or reward magnitude. Significantly higher scores of anxiety sensitivity in GG compared to AG/AA carriers were found only in sample 1. Associations with other personality traits were not observed. Our findings suggest that the rs578776 risk variant influences susceptibility to ND by dampening the response of the anterior cingulate cortex to reward feedback, without recruiting the striatum or orbitofrontal cortex during feedback or anticipation. Thus it seems to have a major role in the processing of and behavioral adaptation to changing reward outcomes.Neuropsychopharmacology accepted article preview online, 21 May 2013; doi:10.1038/npp.2013.131. HubMed – addiction